Protective Effect of Vitamin C on Triptolide-induced Acute Hepatotoxicity in Mice through mitigation of oxidative stress

Protective Effect of Vitamin C on Triptolide-induced Acute Hepatotoxicity in Mice through mitigation of oxidative stress
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维生素 C 通过减轻氧化应激对雷公藤甲素诱发的小鼠急性肝毒性的保护作用

DOI:
10.1590/0001-3765201920181257
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发表时间:
2019-01-01
期刊:
Anais da Academia Brasileira de Ciências
影响因子:
--
通讯作者:
YAN, ZIHANG
YAN, ZIHANG
中科院分区:
其他
文献类型:
--
作者:
XU, PENGJUAN;LI, YOUYOU;YAN, ZIHANG

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雷公藤内酯醇是从雷公藤中提取的二萜类化合物。f.根据权利要求1,被广泛用于治疗多种疾病。然而,雷公藤甲素的肝毒性限制了其临床应用。研究表明氧化应激在雷公藤甲素肝损伤中起重要作用。目的探讨抗氧化剂维生素C对雷公藤甲素肝毒性的影响及其可能机制。在本研究中,通过腹腔注射雷公藤甲素和口服维生素C诱导急性肝损伤。结果表明,维生素C可使肝组织中天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平分别从286.86和746.75 U/mL降至192.48和203.36 U/mL,从而预防雷公藤内酯醇所致的肝损伤。肝脏组织学变化也呈相同趋势。此外,维生素C还通过抑制丙二醛(2.22至1.49 nmol/mgprot)和过氧化氢(14.74至7.19 mmol/gprot)的产生,并恢复总超氧化物歧化酶(24.32至42.55 U/mgprot)和谷胱甘肽(7.69至13.03 μ g/mgprot)的水平,保护肝脏免受雷公藤内酯醇诱导的氧化应激。这些结果表明,维生素C可以通过降低氧化应激来保护雷公藤甲素诱导的肝损伤,维生素C可能在雷公藤甲素的临床使用中具有重要的健康保护作用。
Triptolide, a purified diterpenoid from the herb Tripterygium wilfordii Hook. f., was widely used to treat many diseases. However, the hepatotoxicity of triptolide limited its clinical use. Research showed oxidative stress played an important role in triptolide-induced liver injury. To investigate the effect of vitamin C, which was one of the most effective antioxidants, on triptolide-induced hepatotoxicity and its potential mechanism in mice. In the present study, acute liver injury was induced by intraperitoneal injection of triptolide and vitamin C was orally administered. The results showed treatment with vitamin C prevented the triptolide-induced liver injury by reducing the levels of aspartate transaminase from 286.86 to 192.48 U/mL and alanine aminotransferase from 746.75 to 203.36 U/mL. Histopathological changes of liver corresponded to the same trend. Furthermore, vitamin C also protected the liver against triptolide-induced oxidative stress by inhibiting the generation of malondialdehyde (2.22 to 1.49 nmol/mgprot) and hydrogen peroxide (14.74 to 7.19 mmol/gprot) and restoring the level of total superoxide dismutase (24.32 to 42.55 U/mgprot) and glutathione (7.69 to 13.03 mu g/mgprot). These results indicated that vitamin C could protect against triptolide-induced liver injury via reducing oxidative stress, and vitamin C may pose a significant health protection in the clinical use of triptolide.